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BACKGROUND: In patients with severe COVID-19, no data are available on the longitudinal evolution of biochemical abnormalities and their ability to predict disease outcomes. METHODS: Using a retrospective, longitudinal cohort study design on consecutive patients with severe COVID-19, we used an extensive biochemical dataset of serial data and time-series design to estimate the occurrence of organ dysfunction and the severity of the inflammatory reaction and their association with acute respiratory failure (ARF) and death. FINDINGS: On the 162 studied patients, 1151 biochemical explorations were carried out for up to 59 biochemical markers, totaling 15,260 biochemical values. The spectrum of biochemical abnormalities and their kinetics were consistent with a multi-organ involvement, including lung, kidney, heart, liver, muscle, and pancreas, along with a severe inflammatory syndrome. The proportion of patients who developed an acute kidney injury (AKI) stage 3, increased significantly during follow-up (0·9%, day 0; 21·4%, day 14; P<0·001). On the 20 more representative biochemical markers (>250 iterations), only CRP >90 mg/L (odds ratio [OR] 6·87, 95% CI, 2·36-20·01) and urea nitrogen >0·36 g/L (OR 3·91, 95% CI, 1·15-13·29) were independently associated with the risk of ARF. Urea nitrogen >0·42 g/L was the only marker associated with the risk of COVID-19 related death. INTERPRETATION: Our results point out the lack of the association between the inflammatory markers and the risk of death but rather highlight a significant association between renal dysfunction and the risk of COVID-19 related acute respiratory failure and death.
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Technological progress, including virtual clinics, web or smartphone-based applications, and assessment of fecal calprotectin (FC) at home has favored the implementation of treat to target strategies for patients with inflammatory bowel diseases (IBD). Although these innovations are promising and have been associated with a significant reduction in health costs, their application in clinical practice is limited. Here, we summarize the most recent literature on virtual clinics and available FC home tests. In addition, we report the experience of IBD patients monitored through the IBDoc® test at the Nancy University Hospital, focusing on usability testing and patient's satisfaction. This pilot experience shows that a virtual calprotectin clinic doubles adherence rate to FC in IBD patients. This finding is especially clinically relevant in the post-coronavirus disease 2019 (COVID-19) pandemic era, with an increasing use of e-health.
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BACKGROUND: In patients with severe coronavirus disease 2019 (COVID-19), data are scarce and conflicting regarding whether chronic use of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) influences disease outcomes. In patients with severe COVID-19, we assessed the association between chronic ACEI/ARB use and the occurrence of kidney, lung, heart, and liver dysfunctions and the severity of the inflammatory reaction as evaluated by biomarkers kinetics, and their association with disease outcomes. METHODS: We performed a retrospective longitudinal cohort study on consecutive patients with newly diagnosed severe COVID-19. Independent predictors were assessed through receiver operating characteristic analysis, time-series analysis, logistic regression analysis, and multilevel modeling for repeated measures. RESULTS: On the 149 patients included in the study 30% (44/149) were treated with ACEI/ARB. ACEI/ARB use was independently associated with the following biochemical variations: phosphorus >40 mg/L (odds ratio [OR], 3.35, 95% confidence interval [CI], 1.83-6.14), creatinine >10.1 mg/L (OR, 3.22, 2.28-4.54), and urea nitrogen (UN) >0.52 g/L (OR, 2.65, 95% CI, 1.89-3.73). ACEI/ARB use was independently associated with acute kidney injury stage ≥1 (OR, 3.28, 95% CI, 2.17-4.94). The daily dose of ACEI/ARB was independently associated with altered kidney markers with an increased risk of +25 to +31% per each 10 mg increment of lisinopril-dose equivalent. In multivariable multilevel modeling, UN >0.52 g/L was independently associated with the risk of acute respiratory failure (OR, 3.54, 95% CI, 1.05-11.96). CONCLUSIONS: Patients chronically treated with ACEI/ARB who have severe COVID-19 are at increased risk of acute kidney injury. In these patients, the increase in UN associated with ACEI/ARB use could predict the development of acute respiratory failure.
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Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/virologia , Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , COVID-19/complicações , SARS-CoV-2 , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Feminino , França , Humanos , Rim/efeitos dos fármacos , Rim/virologia , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Análise Multinível , Curva ROC , Encaminhamento e Consulta , Estudos RetrospectivosRESUMO
The SARS-CoV-2 virus is responsible for an epidemic disease called COVID-19, which was initially evidenced in Wuhan, China, and spread very rapidly in China and around the world. In France, the first isolated case seems now to be reported in December 2019, stage 3 of the COVID-19 epidemic was triggered on March 14th, the start of the planned containment exit from May 11th. Healthcare services have faced a large influx of patients who may be beyond their capacity to receive and care, particularly in the Large-East and Ile-de-France regions. Some patients show an evolution of the disease never observed before with other coronaviruses and develop in a few days a very important inflammatory reaction, which can lead to death of patients. A working group of the French Society of Clinical Biology (SFBC) was set up with the objective of providing updated information on the current status of the biological prescriptions (focusing on biochemistry ones) and their evolution during the epidemic, and of analyzing the biological parameters associated with comorbidities and patient evolution in order to link biological results with medical events. The expanded working group covers all sectors of medical biology in France and extends to the French-speaking world: hospital sectors (CHU and CH, Army Training Hospitals) and the private sector opening a field of view on the biological situation in establishments for dependent elderly, social establishments and clinical medical institutions. The purpose of this article is the presentation of this working group and its immediate and future actions.
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Betacoronavirus , Bioquímica/organização & administração , Biomarcadores/análise , Serviços de Laboratório Clínico/organização & administração , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Sociedades Científicas/organização & administração , Betacoronavirus/isolamento & purificação , Betacoronavirus/patogenicidade , Bioquímica/normas , Biomarcadores/sangue , COVID-19 , Serviços de Laboratório Clínico/normas , Redes Comunitárias/organização & administração , Redes Comunitárias/normas , Redes Comunitárias/tendências , Infecções por Coronavirus/sangue , Infecções por Coronavirus/epidemiologia , Surtos de Doenças , França/epidemiologia , História do Século XXI , Humanos , Colaboração Intersetorial , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/epidemiologia , Prática Profissional/organização & administração , Prática Profissional/normas , Prática Profissional/tendências , SARS-CoV-2 , Sociedades Científicas/normas , Comunicação por Videoconferência/organização & administração , Comunicação por Videoconferência/normasRESUMO
BACKGROUND: The diagnosis of iron deficiency is based on ferritin and transferrin saturation (TfS) in inflammatory bowel disease (IBD) patients, yet guideline thresholds are not evidence-based. Soluble transferrin receptor (sTfR) is one of the best noninvasive tests in patients with inflammation. AIMS: To evaluate the accuracy of ferritin and/or TfS for diagnosing iron deficiency in IBD and identify the optimal thresholds of these parameters using sTfR as reference. METHODS: Two hundred and two patients (2072 samples) receiving at least one infusion of biologic (vedolizumab or infliximab) were included. RESULTS: In ulcerative colitis patients with C-reactive protein (CRP) <10 mg/L, optimal iron deficiency diagnostic performances were observed with ferritin and TfS thresholds of 65 µg/L (sensitivity of 0.78 and specificity of 0.76) and 16% (sensitivity of 0.79 and specificity of 0.90), respectively. For ulcerative colitis patients with CRP > 10 mg/L, the thresholds with the best diagnostic performance were 80 µg/L (sensitivity of 0.75 and a specificity of 0.82) for ferritin and 11% for TfS (sensitivity of 0.75 and a specificity of 0.82). There was no added value for combined ferritin and TfS. No ferritin or TfS threshold had good diagnostic performance in Crohn's disease patients (AUC for ferritin was 0.65 (95% CI 0.55-0.75) and the AUC for TfS was 0.70 (95% CI 0.61-0.78). CONCLUSION: Ferritin and TfS are reliable parameters for iron deficiency diagnosis only in ulcerative colitis patients, at thresholds different from current guidelines. In Crohn's disease patients, sTfR should be used given the poor diagnostic performance of ferritin and TfS.
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Anemia Ferropriva/diagnóstico , Ferritinas/sangue , Doenças Inflamatórias Intestinais/sangue , Receptores da Transferrina/sangue , Transferrinas/sangue , Adolescente , Adulto , Anemia Ferropriva/sangue , Anemia Ferropriva/complicações , Produtos Biológicos/uso terapêutico , Biomarcadores/análise , Biomarcadores/sangue , Estudos de Coortes , Feminino , Ferritinas/análise , Humanos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/tratamento farmacológico , Deficiências de Ferro , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Transferrinas/metabolismo , Adulto JovemRESUMO
The original version of this Article contained an error in the title, which was incorrectly given as 'APRDX1 mutant allele causes a MMACHC secondary epimutation in cblC patients'. This has now been corrected in both the PDF and HTML versions of the Article to read 'A PRDX1 mutant allele causes a MMACHC secondary epimutation in cblC patients'.
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To date, epimutations reported in man have been somatic and erased in germlines. Here, we identify a cause of the autosomal recessive cblC class of inborn errors of vitamin B12 metabolism that we name "epi-cblC". The subjects are compound heterozygotes for a genetic mutation and for a promoter epimutation, detected in blood, fibroblasts, and sperm, at the MMACHC locus; 5-azacytidine restores the expression of MMACHC in fibroblasts. MMACHC is flanked by CCDC163P and PRDX1, which are in the opposite orientation. The epimutation is present in three generations and results from PRDX1 mutations that force antisense transcription of MMACHC thereby possibly generating a H3K36me3 mark. The silencing of PRDX1 transcription leads to partial hypomethylation of the epiallele and restores the expression of MMACHC. This example of epi-cblC demonstrates the need to search for compound epigenetic-genetic heterozygosity in patients with typical disease manifestation and genetic heterozygosity in disease-causing genes located in other gene trios.
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Proteínas de Transporte/genética , Epistasia Genética , Erros Inatos do Metabolismo/genética , Mutação , Peroxirredoxinas/genética , Vitamina B 12/metabolismo , Alelos , Azacitidina/farmacologia , Sequência de Bases , Inibidores Enzimáticos/farmacologia , Saúde da Família , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Heterozigoto , Humanos , Masculino , Erros Inatos do Metabolismo/metabolismo , Oxirredutases , Linhagem , Sequenciamento Completo do GenomaRESUMO
BACKGROUND: We investigated, for the first time, levels of compliance with faecal calprotectin test in inflammatory bowel disease patients. METHODS: All consecutive adult inflammatory bowel disease patients having been prescribed an faecal calprotectin test between December 2014-July 2015 were included. At their next visit to the hospital, patients had to return a stool sample for the faecal calprotectin test and answer a simple questionnaire: 'Have you brought a stool sample? If not, why not? If so, did you encounter any difficulties when collecting the sample? Were you aware of faecal calprotectin before being asked to take the test?'. RESULTS: One hundred and one patients were included (50 men; 77 patients with Crohn's disease). The range age was 40 years (19-68). Eighty-nine patients were being treated with infliximab, 10 were on vedolizumab, and two were not being treated with a biologic. Thirty-seven patients (35%) had performed the faecal calprotectin test. Eighty-one patients (80%) had not been aware of faecal calprotectin before being asked to take the test. Of the 64 patients who did not take the test, the prime reasons for non-compliance were forgetfulness (n = 49, 76.6%), a lack of perceived benefit for the test (n = 7, 11%), constipation (n = 5, 7.8%), refusal to handle faeces (n = 2, 3.1%), and difficulty collecting the stool sample (n = 1, 1.5%). CONCLUSION: Only one-third of the patients performed the faecal calprotectin test. The main reason for non-compliance was forgetfulness. Our present results emphasise the need for better patient education on the importance of complying with faecal calprotectin testing and the future of faecal calprotectin testing at home.
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Previous studies have suggested that procalcitonin is a reliable marker for predicting bacteremia. However, these studies have had relatively small sample sizes or focused on a single clinical entity. The primary endpoint of this study was to investigate the diagnostic accuracy of procalcitonin for predicting or excluding clinically relevant pathogen categories in patients with suspected bloodstream infections. The secondary endpoint was to look for organisms significantly associated with internationally validated procalcitonin intervals. We performed a cross-sectional study that included 35,343 consecutive patients who underwent concomitant procalcitonin assays and blood cultures for suspected bloodstream infections. Biochemical and microbiological data were systematically collected in an electronic database and extracted for purposes of this study. Depending on blood culture results, patients were classified into 1 of the 5 following groups: negative blood culture, Gram-positive bacteremia, Gram-negative bacteremia, fungi, and potential contaminants found in blood cultures (PCBCs). The highest procalcitonin concentration was observed in patients with blood cultures growing Gram-negative bacteria (median 2.2âng/mL [IQR 0.6-12.2]), and the lowest procalcitonin concentration was observed in patients with negative blood cultures (median 0.3âng/mL [IQR 0.1-1.1]). With optimal thresholds ranging from ≤0.4 to ≤0.75âng/mL, procalcitonin had a high diagnostic accuracy for excluding all pathogen categories with the following negative predictive values: Gram-negative bacteria (98.9%) (including enterobacteria [99.2%], nonfermenting Gram-negative bacilli [99.7%], and anaerobic bacteria [99.9%]), Gram-positive bacteria (98.4%), and fungi (99.6%). A procalcitonin concentration ≥10âng/mL was associated with a high risk of Gram-negative (odds ratio 5.98; 95% CI, 5.20-6.88) or Gram-positive (odds ratio 3.64; 95% CI, 3.11-4.26) bacteremia but dramatically reduced the risk of PCBCs or fungemia. In this large real-life setting experience with more than 35,000 patients, procalcitonin was highly effective at excluding bloodstream infections regardless of pathogen categories. The results from our study are limited by its cross-sectional design and deserve to be validated in prospective longitudinal studies.
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Bacteriemia/sangue , Bactérias/isolamento & purificação , Calcitonina/sangue , Precursores de Proteínas/sangue , Bacteriemia/diagnóstico , Bacteriemia/microbiologia , Biomarcadores/sangue , Peptídeo Relacionado com Gene de Calcitonina , Estudos Transversais , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos TestesRESUMO
The recent HPST law (reform of the hospital and relative to the patients, to the health and to the territories) states that the formation of the healthcare professionals is now "independent" and "compulsory". This law introduces the term of "Continuous professional development". The "Continuous professional development" groups together the former systems of both Evaluation of the professional practices and in-services training. Indeed, our practice gave us an opportunity to evaluate the practices of the professional of the specialists in laboratory medicine. We had to deal with very unsual cases of interference with a medicine (tenofovir) during the dosage of creatines kinases induced by the presence of a macroenzyme. To achieve this goal, a situation scenario was constructed and sent to a sample of practitioners. The first part deals with a clinical case with an analytic interference provoked by a macroenzyme. The second part refers to the usual techniques employed to reveal the presence of macroenzymes. The results were returned as a document suggesting a way to behave "in front of a suspicion of macroenzymes". This study is an illustration of what can be realized to answer the obligations of continuous professional development.
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Química Clínica , Ensaios Enzimáticos Clínicos , Educação Continuada , Prática Profissional , Adulto , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
Vitamin B9 is represented by the group of folate, whose structure is derived from folic acid. The biologically active form is reduced tetrahydrofolates, serving as an essential cofactor in methylation reactions, including the vitamin B12-dependent formation of methionine from homocysteine, and as a carrier of one-carbon units involved in the synthesis of purines and pyrimidines. Folate deficiency is associated with hyperhomocysteinemia, megaloblastic anemia, leuco- and thrombocytopenia, cardiovascular disease, embryonic defects, in particular neural tube defects, and, possibly, malignancies, depression and cognitive impairment.
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Deficiência de Ácido Fólico , Ácido Fólico/fisiologia , Feminino , Deficiência de Ácido Fólico/diagnóstico , Deficiência de Ácido Fólico/etiologia , Deficiência de Ácido Fólico/terapia , Humanos , Gravidez , Fatores de RiscoRESUMO
The term "vitamin B12" refers to four cobalamins (Cbl), including methyl-Cbl and adenosyl-Cbl, the two enzyme co-factors of methionine synthase and methylmalonyl-CoA mutase, respectively. Vitamin B12 deficiency produces clinical disorders that include mainly megaloblastic anaemia, peripheral and central neurological manifestations. The clinical significance of low blood B12 concentrations in the absence of manifestations of deficiency is a matter of debate. The biochemical diagnosis of the subclinical and clinical deficiency of vitamin B12 has been enriched by several parameters, including serum methylmalonic acid, homocysteine, and holo-transcobalamine, which have been evaluated over the past two decades.
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Deficiência de Vitamina B 12 , Vitamina B 12/fisiologia , Humanos , Distúrbios Nutricionais/diagnóstico , Distúrbios Nutricionais/etiologia , Distúrbios Nutricionais/terapia , Vitamina B 12/sangue , Deficiência de Vitamina B 12/diagnóstico , Deficiência de Vitamina B 12/etiologia , Deficiência de Vitamina B 12/terapiaAssuntos
Creatina Quinase Forma MB/análise , Creatina Quinase/análise , Infecções por HIV/enzimologia , Adenina/análogos & derivados , Adenina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Creatina Quinase/química , Creatina Quinase/metabolismo , Creatina Quinase Forma MB/química , Creatina Quinase Forma MB/metabolismo , Eletroforese , Infecções por HIV/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Ácidos Fosforosos/uso terapêutico , Estudos Retrospectivos , Inibidores da Transcriptase Reversa/uso terapêutico , Adulto JovemRESUMO
The treatment of renal anaemia with erythropoiesis stimulating agent is often associated with a functional iron deficiency characterized by normal or elevated iron stores but insufficient iron delivered for erythropoiesis. Biological markers of iron status depend on the compartment where it is located: stored, circulating or available for erythropoiesis. Ferritin is the protein of iron storage but also a protein of the acute phase of inflammation and serum ferritin increases in case of liver cytolysis. In the circulation iron is bound to transferrin (Tf). Tf dosage is necessary to calculate transferrin saturation coefficient (TSAT) which decreases below 20% in iron deficiency but also in inflammatory states. Another Limitation is the nycthemeral variations of serum iron. The best marker of functional iron deficiency is the percentage of hypo chromic red cells (> 6%) followed by reticulocyte Hb content (< 29 pg/cell). These 2 markers measure the body capacity to donate iron to erythroid precursors but necessitate specific laboratory equipment. In all cases evaluation of iron balance should be done at least eight days after the last iron infusion.
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Anemia/tratamento farmacológico , Eritropoese/efeitos dos fármacos , Ferritinas/sangue , Hematínicos/uso terapêutico , Ferro/sangue , Falência Renal Crônica/terapia , Anemia/classificação , Anemia/etiologia , Biomarcadores , Humanos , Falência Renal Crônica/complicações , Diálise RenalRESUMO
Traditionally, the standard biochemical markers of iron status are serum iron, transferrin, transferrin saturation, ferritin and, more recently, soluble transferrin receptor. Diagnosis of iron deficiency is usually associated with a low serum ferritin concentration. The diagnosis can be difficult in diseases in which there is an acute-phase response, because ferritin is an acute-phase reactant. In this case, measuring soluble transferrin receptor may be useful because an increased concentration is an indicator of iron deficiency. Iron stores are frequently diminished in patients on dialysis, as a result of increased blood loss and poor iron absorption. Demand for available iron is increased further by the use of erythropoietin and iron deficiency is one of the primary causes for decreased response to recombinant human erythropoeitin therapy (rHuEpo). Prevalence of inflammation in patients on dialysis is estimated to be high (as 50% patients). Because ferritin is an acute-phase reactant, levels may be elevated in cases of inflammation. The aim of recent guidelines is to better assess anaemia and iron stores. Serum ferritin and transferrin saturation are regarded as the most reliable indicators of iron status. A newer alternative laboratory measurement is the soluble transferrin receptor. Some authors suggest that the circulating soluble transferring receptor levels may be useful in monitoring iron status in patients on dialysis if rHuEpo doses are maintained constant. Prospective longitudinal studies are needed to evaluate this hypothesis.